The goals of this project are to characterize the nature and mode of action of suppressor cells in the peripheral blood of normal humans and in humans with depressed cellular immunity. In particular we are studying the prostaglandin producing suppressor cell, a glass adherent mononuclear cell that secretes prostaglandin E2 (PGE2) which in turn suppresses the T-cell response to mitogen and antigen in vitro. We have studied the role of the PG producing suppressor cell in the depressed cellular immunity associated with several human disease states. In Hodgkin's Disease increased activity of this cell appears to be responsible for the depressed mitogen response. The depressed mitogen response in patients with sarcoidosis is due to a glass adherent suppressor cell other than the prostaglandin producing suppressor cell. Indomethacin (a prostaglandin synthetase inhibitor) will reverse the depressed mitogen response in patients with common variable hypogammaglobulinemia in vitro, and whenthe drug is given orally to these anergic patients they become reactive to skin testing. We have continued our studies on binding sites for prostaglandins on human lymphocytes, and have identified a high affinity binding site for PGE2. The Kd approximately equals 2 times 10 minus 9th power with approximately 200 binding sites per cell, assuming uniform distribution. This PGE2 receptor appears to be linked to adenyl cyclase.